Connective tissue is an important biological tissue composed of an extracellular matrix that binds, anchors, and supports organs. There are various types of connective tissue, all of which consist of varying combinations of fibers, cells, and intercellular substance. Over 200 conditions, which may be inherited or autoimmune, affect connective tissue, and they are collectively known as connective tissue diseases (CTDs). Inherited CTDs are caused by mutations that affect one of the two fibers (collagen and fibrillin). Autoimmune CTDs have no clear etiology, but the incidence is higher in women and among genetically predisposed individuals. As the name suggests, in autoimmune CTDs, the immune system develops antibodies against components of connective tissue. Individual conditions can affect a vast range of bodily structures (including cartilage, blood vessels, bone, tendons, and organs) and thus present with a wide array of clinical findings.
Autoimmune connective tissue diseases
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Inflammatory myopathies (e.g., polymyositis; , dermatomyositis)
- Systemic sclerosis
- Sjogren syndrome
- Mixed connective tissue disease (Sharp's syndrome)
- An immune system disorder characterized by inflammation in cartilaginous structures (e.g., eyes, nose, ears, joints, respiratory tract).
- Manifestations include episcleritis, saddle nose deformity, obstruction lung disease, and arthralgia.
Inherited connective tissue diseases
- Ehlers-Danlos syndrome
- Marfan syndrome
- Osteogenesis imperfecta
- Alport syndrome
Loeys-Dietz syndrome 
- Autosomal dominant inheritance
- Caused by mutations in TGFβ receptor
- Features shared with Marfan syndrome: marfanoid habitus, increased risk of ascending aortic aneurysms and aortic dissection
- Distinct features: hypertelorism, bifid uvula, cleft palate, easy bruising and keloids, arterial tortuosity (winding course of arteries)
- Autosomal dominant inheritance
- Caused by mutations in COL2A1 gene leading to impaired production of type 2 collagen
- Clinical features
- Short stature
- Ocular disorders (e.g., myopia, cataracts)
- Hearing impairment
Clinical manifestations of connective tissue disorders
Clinical features vary greatly among individual diseases. The table below provides a general overview of the more common features.
|Overview of manifestations of connective tissue disorders|
|Features||Autoimmune CTDs||Inherited CTDs|
|General|| || |
|Musculoskeletal|| || |
|Other organ manifestations|| |
Connective tissue disorders
This table lists the most important connective tissue disorders and some examples of their clinical features. For more information on Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta, see the respective articles.
|Overview of inherited connective tissue disorders|
|Condition||Etiology||Pathophysiology||Clinical features (examples)|
|Marfan syndrome|| || || |
|Ehlers-Danlos syndrome|| || || |
|Menkes disease || || || |
|Osteogenesis imperfecta|| || || |
|Scurvy|| || || |
A for Absent copper and B for a Bunch of copper: In Menkes disease, the ATP7A gene is defective, resulting in decreased copper levels. In Wilson disease, the ATP7B gene is defective, which leads to high copper levels.
Ehlers-Danlos syndrome and Menkes disease are both associated with reduced lysyl oxidase activity, resulting in defective collagen cross-linking and fibril synthesis.